Department of Hematology and Oncology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Escuela de Medicina, Universidad Panamericana, Mexico City, Mexico.
BMC Cancer. 2020 Sep 14;20(1):882. doi: 10.1186/s12885-020-07383-2.
Cytotoxic chemotherapy can cure advanced germ cell tumors. Nevertheless, cancer treatment may induce cellular senescence and accelerate molecular aging. The aging process implies an increase of cells expressing p16 and changes in lymphocyte subpopulations. Our aim was to study the potential induction of premature immunosenescence in testicular cancer survivors (TCS) exposed to chemotherapy.
Case-control exploratory study of TCS treated with chemotherapy (≥3 BEP cycles, disease-free ≥3 months) compared with age matched healthy controls. Peripheral blood mononuclear cells were isolated, and lymphocyte subpopulations were analyzed by flow cytometry. CDKN2A/p16 expression in T cells was measured using qPCR. The percentage of lymphocyte subpopulations and the CDKN2A/p16 expression in TCS were compared with the control group using the Wilcoxon signed-rank test.
We included 16 cases and 16 controls. The median age was 27 years (minimum 24, maximum 54) and the median time on surveillance was 26.5 months (minimum 3, maximum192). TCS had a lower percentage of total T cells and CD4+ T cells in total lymphocytes. Among the CD4+ T lymphocytes, TCS had less naïve CD4+ and increased memory CD4+ cells. Within the CD8+ T lymphocytes, TCS exhibited a decrease in the percentage of naïve cells and an increase in CD8 + CD45RA + CD57+ cells. TCS also exhibited decreased memory CD19+ B cells compared to the controls. The relative expression of CDKN2A/p16 in T cells was increased in TCS (mean 1.54; 95% CI of the mean: 1.074-2.005; p = 0.048).
In this exploratory study, TCS showed increased expression of CDKN2A/p16 and a lymphocyte phenotype that has been associated with immunosenescence. Further studies are warranted to define the clinical implications of these alterations in TCS.
细胞毒性化疗可治愈晚期生殖细胞肿瘤。然而，癌症治疗可能会诱导细胞衰老并加速分子衰老。衰老过程意味着表达 p16 的细胞增多和淋巴细胞亚群发生变化。我们的目的是研究接受化疗的睾丸癌幸存者（TCS）中潜在的过早免疫衰老的诱导。
对接受化疗（≥3 个 BEP 周期，无病≥3 个月）的 TCS 进行病例对照探索性研究，并与年龄匹配的健康对照组进行比较。分离外周血单核细胞，并通过流式细胞术分析淋巴细胞亚群。使用 qPCR 测量 T 细胞中 CDKN2A/p16 的表达。使用 Wilcoxon 符号秩检验比较 TCS 与对照组之间淋巴细胞亚群和 CDKN2A/p16 的表达百分比。
我们纳入了 16 例病例和 16 例对照。中位年龄为 27 岁（最小 24 岁，最大 54 岁），中位随访时间为 26.5 个月（最小 3 个月，最大 192 个月）。TCS 在总淋巴细胞中总 T 细胞和 CD4+T 细胞的百分比较低。在 CD4+T 淋巴细胞中，TCS 的幼稚 CD4+细胞减少，记忆性 CD4+细胞增加。在 CD8+T 淋巴细胞中，TCS 表现为幼稚细胞百分比降低，CD8+CD45RA+CD57+细胞增加。与对照组相比，TCS 中记忆性 CD19+B 细胞也减少。T 细胞中 CDKN2A/p16 的相对表达在 TCS 中增加（平均 1.54；均值的 95%置信区间：1.074-2.005；p=0.048）。
在这项探索性研究中，TCS 表现出 CDKN2A/p16 的表达增加和与免疫衰老相关的淋巴细胞表型。需要进一步研究以确定这些 TCS 改变的临床意义。
